Bidirectional regulation of free fatty acid receptors and non-alcoholic fatty liver disease.

Free fatty acid receptor action is primarily in the area of energy modulation and maintenance of normal metabolism in the body. They have been identified and attributed to specific G protein-coupled receptors (GPCRs). Currently, the main findings include four receptors: FFAR1 to FFAR4. Free fatty acids (FFAs) with different carbon chain lengths respond to different FFAR. Short-chain fatty acids (C2-C6) bind specifically to FFAR2 and FFAR3, whereas medium-chain fatty acids (C6-C12) and long-chain fatty acids (C13-C21) target both FFAR1 and FFAR4. FFARs have been considered as potential target for the treatment of common metabolic diseases such as T2M, cardiovascular diseases and inflammatory bowel diseases. Nonalcoholic fatty liver disease is a common metabolic disorder and is often accompanied by various metabolic and cardiovascular diseases. The expression and modulation of FFARs in the body may be related to the development of nonalcoholic fatty liver disease. This article introduces the source, synthesis and metabolic pathways of fatty acids, and comprehensively summarizes the research on FFARs signal transduction and its physiological functions, the regulation between FFARs and NAFLD, and the prospect of FFARs-based treatment of NAFLD.

• Publication year

  2025

• Venue

  Journal of Nutritional Biochemistry

• Publication date

  2025-11-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.jnutbio.2025.110180PMID 41224148
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Glycerolipid Cycling in Thermogenesis, Energy Homeostasis and Signaling.

  2025cited by this paper
• A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis.

  2024cited by this paper
• First US drug approved for a liver disease surging around the world.

  2024cited by this paper
• Lean individuals with NAFLD have more severe liver disease and poorer clinical outcomes (NASH-CO Study)

  2023cited by this paper
• Mechanism of action of the bile acid receptor TGR5 in obesity

  2023cited by this paper
• Progress in the Treatment of Metabolic-Related Fatty Liver Disease.

  2023cited by this paper
• Type 2 Diabetes Mellitus, Non-Alcoholic Fatty Liver Disease, and Metabolic Repercussions: The Vicious Cycle and Its Interplay with Inflammation

  2023cited by this paper
• The Microstructure, Antibacterial and Antitumor Activities of Chitosan Oligosaccharides and Derivatives

  2022cited by this paper
• Short-Chain Fatty Acid Receptors and Cardiovascular Function

  2022cited by this paper
• The role and mechanism of CREBH regulating SIRT3 in metabolic associated fatty liver disease.

  2022cited by this paper
• Noni (Morinda citrifolia L.) fruit phenolic extract supplementation ameliorates NAFLD by modulating insulin resistance, oxidative stress, inflammation, liver metabolism and gut microbiota.

  2022cited by this paper
• Non-Alcoholic Fatty Liver Disease (NAFLD) Pathogenesis and Natural Products for Prevention and Treatment

  2022cited by this paper
• Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: An updated meta-analysis with 135,602 individuals

  2022cited by this paper
• TyG index is positively associated with risk of CHD and coronary atherosclerosis severity among NAFLD patients

  2022cited by this paper
• Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways

  2022cited by this paper
• Non-Alcoholic Fatty Liver Disease, Insulin Resistance, Metabolic Syndrome and their Association with Vascular Risk.

  2021cited by this paper
• Nutrigenomics and Nutrigenetics in Metabolic- (Dysfunction) Associated Fatty Liver Disease: Novel Insights and Future Perspectives

  2021cited by this paper
• Diet and exercise in NAFLD/NASH: Beyond the obvious

  2021cited by this paper
• Insulin Resistance: From Mechanisms to Therapeutic Strategies

  2021cited by this paper
• Short-Chain Fatty Acids, Maternal Microbiota and Metabolism in Pregnancy

  2021cited by this paper
• Free Fatty Acid Receptors in Health and Disease.

  2020cited by this paper
• Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid-Mediated Activation of G Protein-Coupled Receptors GPR43 and GPR109A.

  2020cited by this paper
• Effects of the Mediterranean diet on cardiovascular risk factors in non-alcoholic fatty liver disease patients: A systematic review and meta-analysis.

  2020cited by this paper
• Gut microbiota-derived metabolites as key actors in inflammatory bowel disease

  2020cited by this paper
• GPR40-Deficiency Is Associated with Hepatic FAT/CD36 Upregulation, Steatosis, Inflammation and Cell Injury in C57BL/6 Mice.

  2020cited by this paper
• The Impact of Non-alcoholic Fatty Liver Disease in Primary Care: A Population Health Perspective.

  2020cited by this paper
• Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism

  2020cited by this paper
• ZLY032, the first-in-class dual FFA1/PPARδ agonist, improves glucolipid metabolism and alleviates hepatic fibrosis.

  2020cited by this paper
• Effects of combined therapy with resveratrol, continuous and interval exercises on apoptosis, oxidative stress, and inflammatory biomarkers in the liver of old rats with non-alcoholic fatty liver disease

  2019cited by this paper
• Free Fatty Acid Receptors as new potential therapeutic target in Inflammatory Bowel Diseases.

  2019cited by this paper
• Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study

  2019cited by this paper
• n-3 Polyunsaturated fatty acids for the management of alcoholic liver disease: A critical review

  2019cited by this paper
• Diet and Non-Alcoholic Fatty Liver Disease: The Mediterranean Way

  2019cited by this paper
• The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat

  2018cited by this paper
• NAFLD AND NASH: Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention

  2018cited by this paper
• Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra‐Virgin Olive Oil or Nuts

  2018cited by this paper
• The PI3K/AKT pathway in obesity and type 2 diabetes

  2018cited by this paper
• Butyrate Modulates Inflammation in Chondrocytes via GPR43 Receptor

  2018cited by this paper
• Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease

  2018cited by this paper
• Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease.

  2018cited by this paper
• DHA supplementation prevent the progression of NASH via GPR120 signaling

  2018cited by this paper
• Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug

  2017cited by this paper
• Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity

  2017cited by this paper
• Free Fatty Acid Receptor 4 Mediates the Beneficial Effects of n-3 Fatty Acids on Body Composition in Mice

  2017cited by this paper
• Free‐fatty acid receptor‐4 (FFA4) modulates ROS generation and COX‐2 expression via the C‐terminal &bgr;‐arrestin phosphosensor in Raw 264.7 macrophages

  2017cited by this paper
• Maternal High Fiber Diet during Pregnancy and Lactation Influences Regulatory T Cell Differentiation in Offspring in Mice

  2017cited by this paper
• Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.

  2017cited by this paper
• Nutritional Approaches to Achieve Weight Loss in Nonalcoholic Fatty Liver Disease.

  2017cited by this paper
• The role and regulation of the peroxisome proliferator activated receptor alpha in human liver.

  2017cited by this paper
• Clinical epidemiology and disease burden of nonalcoholic fatty liver disease

  2017cited by this paper
• Free-fatty acid receptor-4 (GPR120): Cellular and molecular function and its role in metabolic disorders.

  2016cited by this paper
• Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity.

  2016cited by this paper
• GPR41 modulates insulin secretion and gene expression in pancreatic β‐cells and modifies metabolic homeostasis in fed and fasting states

  2016cited by this paper
• Global epidemiology of nonalcoholic fatty liver disease—Meta‐analytic assessment of prevalence, incidence, and outcomes

  2016cited by this paper
• Prospective association of the Mediterranean diet with cardiovascular disease incidence and mortality and its population impact in a non-Mediterranean population: the EPIC-Norfolk study

  2016cited by this paper
• The Intestinal Microbiota in Metabolic Disease

  2016cited by this paper
• Nutritional Signaling via Free Fatty Acid Receptors

  2016cited by this paper
• Lipotoxic lethal and sublethal stress signaling in hepatocytes: relevance to NASH pathogenesis[S]

  2016cited by this paper
• Metabolism meets immunity: The role of free fatty acid receptors in the immune system.

  2016cited by this paper
• Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD

  2016cited by this paper
• Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites

  2015cited by this paper
• Potential for dietary ω-3 fatty acids to prevent nonalcoholic fatty liver disease and reduce the risk of primary liver cancer.

  2015cited by this paper
• Monounsaturated Fatty Acid–Enriched High-Fat Diets Impede Adipose NLRP3 Inflammasome–Mediated IL-1β Secretion and Insulin Resistance Despite Obesity

  2015cited by this paper
• FFAR3 modulates insulin secretion and global gene expression in mouse islets

  2015cited by this paper
• De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose

  2015cited by this paper
• Proton magnetic resonance spectroscopy reveals increased hepatic lipid content after a single high-fat meal with no additional modulation by added protein.

  2015cited by this paper
• The natural history of cirrhosis from parenteral nutrition-associated liver disease after resolution of cholestasis with parenteral fish oil therapy.

  2015cited by this paper
• A journey into a Mediterranean diet and type 2 diabetes: a systematic review with meta-analyses

  2015cited by this paper
• Tumor necrosis factor α decreases glucagon-like peptide-2 expression by up-regulating G-protein-coupled receptor 120 in Crohn disease.

  2015cited by this paper
• Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes

  2015cited by this paper
• Activation of Extracellular Signal-Regulated Protein Kinases 1 and 2 (ERK1/2) by Free Fatty Acid Receptor 1 (FFAR1/GPR40) Protects from Palmitate-Induced Beta Cell Death, but Plays no Role in Insulin Secretion

  2015cited by this paper
• Plasma fatty acid composition in French-Canadian children with non-alcoholic fatty liver disease: Effect of n-3 PUFA supplementation.

  2015cited by this paper
• Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion.

  2015cited by this paper
• Diets Containing α-Linolenic (ω3) or Oleic (ω9) Fatty Acids Rescues Obese Mice From Insulin Resistance.

  2015cited by this paper
• Omega-3 Fatty Acids and FFAR4

  2014cited by this paper
• GPR120 on Kupffer cells mediates hepatoprotective effects of ω3-fatty acids.

  2014cited by this paper
• GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans

  2014cited by this paper
• A Gpr120 Selective Agonist Improves Insulin Resistance and Chronic Inflammation

  2014cited by this paper
• The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes

  2014cited by this paper
• Gut microbiota and energy balance: role in obesity

  2014cited by this paper
• Diets and nonalcoholic fatty liver disease: the good and the bad.

  2014cited by this paper
• The SCFA Receptor GPR43 and Energy Metabolism

  2014cited by this paper
• Overfeeding Polyunsaturated and Saturated Fat Causes Distinct Effects on Liver and Visceral Fat Accumulation in Humans

  2014cited by this paper
• N-3 long-chain PUFA supplementation prevents high fat diet induced mouse liver steatosis and inflammation in relation to PPAR-α upregulation and NF-κB DNA binding abrogation.

  2014cited by this paper
• Reversal of high-fat diet-induced hepatic steatosis by n-3 LCPUFA: role of PPAR-α and SREBP-1c.

  2014cited by this paper
• Non-alcoholic fatty liver disease, obesity and the metabolic syndrome.

  2014cited by this paper
• Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty liver disease.

  2014cited by this paper
• Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis

  2014cited by this paper
• The Negative Effects of Obesity and Poor Glycemic Control on Cognitive Function: A Proposed Model for Possible Mechanisms

  2014cited by this paper
• Nonalcoholic fatty liver disease: A main driver of insulin resistance or a dangerous liaison?

  2014cited by this paper
• The fish oil ingredient, docosahexaenoic acid, activates cytosolic phospholipase A2 via GPR120 receptor to produce prostaglandin E2 and plays an anti‐inflammatory role in macrophages

  2014cited by this paper
• Free fatty acid receptor 2, a candidate target for type 1 diabetes, induces cell apoptosis through ERK signaling.

  2014cited by this paper
• International Union of Basic and Clinical Pharmacology. LXXXVIII. G Protein-Coupled Receptor List: Recommendations for New Pairings with Cognate Ligands

  2013cited by this paper
• The Pharmacology of TUG-891, a Potent and Selective Agonist of the Free Fatty Acid Receptor 4 (FFA4/GPR120), Demonstrates Both Potential Opportunity and Possible Challenges to Therapeutic Agonism

  2013cited by this paper
• Metabolic signaling in fuel-induced insulin secretion.

  2013cited by this paper
• Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells.

  2013cited by this paper
• The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43

  2013cited by this paper
• Docosahexaenoic acid for the treatment of fatty liver: randomised controlled trial in children.

  2013cited by this paper
• Reevaluation of Fatty Acid Receptor 1 as a Drug Target for the Stimulation of Insulin Secretion in Humans

  2013cited by this paper
• β-Arrestin 2 mediates G protein-coupled receptor 43 signals to nuclear factor-κB.

  2013cited by this paper

• No citing papers are available for this paper.